"Determining when hypofractionation should be used can be challenging and some proposed methodologies are complicated," Hiram Gay, an assistant professor based at Washington University School of Medicine (St Louis, MO), told medicalphysicsweb. "Our method is a universal way to evaluate treatment plans and hinges on the simple division of two numbers. We can determine the mathematical boundary where there is an advantage or disadvantage for hypofractionation depending on the context: tumour treatment or normal tissue sparing."

Finding the advantage

Today, many alternative treatment strategies are being explored in an attempt to improve upon the results that can achieved with conventional radiotherapy. Such strategies include the likes of combined chemoradiotherapy, the use of protons or carbon ions, and hypofractionation, where fewer fractions are used to deliver the same total dose.

As hypofractionation has already proved useful in treating cancer at sites such as the lung, breast and prostate, the team's goal was to provide a simple relationship that clinicians could use to help them visually determine the areas and volumes in a treatment plan where hypofractionation is most advantageous.

The starting point for Gay and his collaborators was to consider two fractionation regimes. These regimes had a different number of fractions and a different dose per fraction, but based on the linear quadratic model, should result in the same biologically effective dose (BED) to an arbitrary tumour or normal structure. The desired end-point was a simple relationship to illustrate situations and treatment plan regions where hypofractionation or standard fractionation might be preferred.

"We have included an appendix in our paper to show how this massively complicated mathematical problem can be simplified," commented Gay. "The normal tissue isodose boundary that determines where the advantage or disadvantage in performing hypofractionated therapy lies is simply the normal tissue α/β-ratio divided by the tumour α/β-ratio – multiplied by 100 if you would like the answer as a percentage."

Applying the relationship

Gay and his collaborators subsequently used their method to illustrate the potential BED, isodose and fractionation implications on normal tissue sparing for prostate and lung tumours.

"Our take-home message is that if a treatment plan can achieve sharp gradients (dose drop) between the tumour and normal tissues, you are more likely to achieve an advantage for hypofractionation," said Gay. "Optimal lung plans taking advantage of hypofractionation should for example have the isodose drop from 100% to 30% in the shortest possible distance."

The slight limitation of the method is finding an accurate measure of the α/β-ratios for tumour and normal tissues. "In some cases, these parameters have good estimates," said Gay. "Normal tissue ratios tend to be more predictable while tumour ratios have more variability. Hopefully in the future we can provide better and individualized estimates through genetic testing making the technique both tissue- and patient-specific."

In the shorter term, Gay is now hoping to explore hypofractionation for treating other tumour types and locations, such as renal cell carcinoma kidney masses, palliative treatment of large tumour masses in the abdomen and pelvis, treatment of prostate cancer, and specific situations in head-and-neck cancer.